2,5-disubstituted 1,3,4-thiadiazoles

ABSTRACT

This invention relates to novel 5-amino, 5-acetamido and 5nitro-2-substituted 1,34-thiadiazoles and their derivatives. These compounds are useful as antibacterial or antifungal agents.

Uiliififi statfiS Patent 1 Berkelhammer et a1.

[ 1 Apr. 3, 1973 [54] 2,5-DISUBSTITUTED 1,3,4-

THIADIAZOLES [75] lnventors: Gerald Berkelhammer, Princeton;

" Goro Asato, Titusville, both of NJ.

[73] Assignee: American Cyanamid Company,

Stamford, Conn.

[52] US. Cl "260/240 G, 424/258, 424/270, 260/240 E, 260/240.9, 260/302 H, 260/3068 D [51] Int. Cl. ..C07d 91/62 [58] Field of Search ..260/302 D, 240 E, 306.8 D,

[56] References Cited UNITED STATES PATENTS 3,598,830 8/1971 Berkelhammer etal. ..260/302 D FOREIGN PATENTS OR APPLICATIONS 1,231,934 4/1960 France ..260/306.8 D

OTHER PUBLICATIONS Ohta et al, Chemical Abstracts, Vol. 48, cols. 10006 to 10007 (1954) Ohta, Chemical Abstracts, Vol. 48, col. 12091 (1954) Maffi et al., Chemical Abstracts, Vol. 53, col. 2211 (1959) Arnold, Ber. Deut. Chem., Vol. 75 (B), pages 87 and 89 (1942).

Primary Examiner-John D. Randolph Attorney-Ernest Y. Miller [5 7] ABSTRACT This invention relates to novel S-amino, S-acetamido and 5-nitro-2-substituted 1,34-thiadiazoles and their derivatives, These compounds are useful as antibacterial or antifungal agents.

7 Claims, No Drawings 2,5-DISUBSTITUTED 1,3,4-TIIIADIAZOLES This application is a division of our application Ser. No. 767,004, filed Oct. 11, 1968, now US. Pat. No. 3,598,830.

SUMMARY OF THE INVENTION The present invention relates to novel thiadiazole compounds, a method for their preparation and a method of use for controlling bacteria and fungi, par- 1 ticularly plant pathogenic bacteria and fungi. More particularly, the novel compounds of the invention have the formula:

l lmto...

In the preparation of the present compounds as shown in the flowsheets and examples hereinafter set forth three essential starting materials are used. The first of these is S-nitro-l,3,4-thiadiazole-2-carboxaldehyde, the product of Examples 1 and 4, and described in the flow diagrams as compound (IV). The second is S-amino-l,3,4-thiadiazole-2-carboxaldehyde, the product of Example 3, identified as compound (III) in the flow diagrams and 5-acetamido-l,3,4- thiadiazole-2-carboxaldehyde, the product of Example 11 and referred to in the flow diagrams as compound (XI).

In accordance with the invention and referring to flow diagram I, S-nitro-l ,3,4-thiadiazole-2-carboxaldehyde (IV) can be prepared by oxidation of 2-methyl- 5-nitro-l,3,4-thiadiazole (I) at high temperature. The reaction is preferably carried out in the presence of an inert organic solvent and employing an oxidizing agent such as, for example, selenium dioxide. Said compound (IV) may also be prepared from S-amino-l ,3,4- thiadiazole-2-carboxaldehyde (III) by formation of the aldehyde di-azonium salt followed by reaction with excess alkali metal nitrite in the presence of a copper catalyst.

The 5-nitro-2-thiadiazole-carboxaldehyde (IV) may then be converted to 3-{[(5-nitro-l,3,4-thiadiazol-2- yl)methylene]-amino} -2-oxazolidinone (V), I-{[(5- nitro-l ,3 ,4-thiadiazol-2-yl)-methylene]amino} -2- imidazolidinone (VI) or S-nitro-l,3,4-thiadiazole-2- carboxaldehyde thiosemicarbazone (VII) by reaction of the above said carboxaldehyde (IV) with 3-amino-2- oxazolidinone l-amino-2-imidazolidinone or thiosemicarbazide, respectively. The reactions are preferably conducted in an alcoholic or aqueous-alcoholic medium at an elevated temperature, generally between about C. and C. and under slightly acidic conditions. Mineral acids such as hydrochloric and sulfuric acid are well adapted to use in these reactions.

Similarly, treatment of 5-aminol,3,4-thiadiazole-2- carboxaldehyde (III) (Flow Diagram II) or 5- acetamido-l,3,4-thiadiazole-2-carboxaldehyde (XI) (Flow Diagram III) with l-amino-2-imidazolidinone, 3- amino-2-oxazolidinone or thiosemicarbazide, under acid conditions at an elevated temperature, yields respectively, the corresponding l-{[(5-amino-l,3,4- thiadiazol-Z-yl)methylene ]amino} -2-imidazolidinone ]amino} -2-oxazolidinone (XV), 5-amino-1,3 ,4- thiadiazolecarboxaldehyde thiosemicarbazone (XVII), and l- S-acetamido-l ,3 ,4-thiadiazol-2-yl)methylene ]amino}-2-imida-zolidinone (XIII), 3-{[(5-acetamidol ,3 ,4-thiadiazol-2-yl )methylene ]amino} -2 -oxazolidinone (XIV), and S-acetamido-l ,3,4-thiadiazole- 2-carboxaldehyde thiosemicarbazone (XVI).

Cyclization of S-nitro-I,3,4-thiadiazole-2-carboxaldehyde thiosemicarbazone (VII), (Diagram I), 5- amino-l ,3 ,4-thiadiazolecarboxaldehyde thiosemicarbazone (XVII), (Diagram II), and 5-acetamido-l,3,4- thiadiazole-2-carboxaldehyde thiosemicarbazone XVI), (Diagram III), to the corresponding aminothiadiazoles can then be achieved by treatment of said thiosemicarbazones with an oxidative cyclizing agent such as ferric ammonium sulfate, ferric chloride or ferric sulfate, at an elevated temperature preferably between about 70C. and 115C. in water or aqueous alcohol.

Treatment of the cyclized bis amino compound (X- VIII) (Diagram II) with acetic anhydride at high temperature, yields the corresponding bis acetamido compound (XIX When the S-nitro- (IV) or 5-acetamido-l,3,4- thiadiazole carboxaldehydes (XI) are reacted with quinaldine and acetic anhydride under acid conditions and high temperature the corresponding thiadiazol-Z-yl vinyl'quinolines, (XX) and (XXI) respectively, are formed. However, the S-amino carboxaldehyde (III) does not undergo the same relation to form the corresponding S-amino vinyl quinoline, but rather, yields the S-acetamido vinyl quinoline (XXI) which is converted by acid hydrolysis to the 2-[2-(5-amino-l,3,4- thiadiazol-Z-yl)vinyllquinoline (XXII), (Diagram III).

In Flow Diagram (II) it can be seen that S-aminol,3,4-thiadiazole-Z-carboxaldehyde (III) may be obtaining by first refluxing p-nitrobenzaldehyde with 2- acetamido-S-methylthiadiazole in acetic anhydride to obtain nitrostyrene (II) and ozonizing such product in the presence of ethyl acetate to yield a crude product containing 5 -acetamido-l ,3 ,4-thiadiazole-2-carboxaldehyde (XI) which may be hydrolyzed to S-aminol,3,4-thiadiazole-2-carboxaldehyde (III) under acid conditions. If desired, the 5-acetamido-l,3,4- thiadiazole-2-carboxaldehyde (XI) may also be obtained from 5-amino-l,3,4 -thiadiazole-2-carboxaldehyde (III) by refluxing with acetic anhydride.

The following flow diagrams I, II and III, illustrate the reactions described hereinabove.

3-{[(5-amin o-l,3,4-thiadiazol-2-yl)methylene FLOW DIAGRAM II-Continued XIX FLOW DIAGRAM III The compounds of the present invention are useful as antibacterial and antifungal agents. They find utility in such areas as treatment of industrial process waters used for cooling equipment and in paper manufacture to control slimes. Generally about l to 500 ppm. of the compounds of the present invention are effective for this purpose. As indicated, these compounds are also useful for protecting fabrics, textiles, leather and the like as well as agronomic crops, both growing and harvested, from the deleterious effects of these organisms.

In practice the compounds of the invention may be formulated with both solid and liquid diluents and applied in the form of dusts and sprays to the materials or plants for which protection is sought.

Dust formulations are generally prepared by admixing about 1 to 25 percent by weight of active compound with a finely divided carrier such as kaolin, attapulgite, diatomaceous earth, talc or the like and can be applied with conventional dusting apparatus. For protection of growing plants generallyabout Mb. to 8 lbs. per acre of active ingredient is sufficient but somewhat higher rates may be employed if so desired.

Wettable powder formulations which are generally dispersed in an inexpensive liquid carrier, such as water or deodorized kerosene, for spray application, are usually prepared by admixing about 25 to 90 percent by weight of active ingredient with about to percent of a solid diluent, as described above with regard (CHQCOMO IICl cmcoon XVI XXII

XXIII to dust formulation, about 1 to 3 percent of a wetting agent and about 2 to 5 percent of a dispersant. For ap- DETAILED DESCRIPTION The following examples describe the preparation of the present compounds and tests as antibacterial and anti-fungal agents.

EXAMPLE 1 Preparation of S-Nitro-l ,3,4-thiadiazole-2- carboxaldehyde (IV) The compound 2-methyl-5-nitro-l,3,4-thiadiazole (l) (0.73 g. or 5 mmole) and 0.55 g. (5 mmole) of selenium dioxide are mixed and heated until a highly exothermic reaction occurs. The mixture is cooled and extracted with methylene chloride. The extracts are dried and evaporated to dryness to give a red-brown liquid, which is the title compound; infraredspectrum (neat): 1700 (C=O), 1565 and 1355 (NO,) cmf.

EXAMPLE 2 Preparation of B-(S-Acetamido-l ,3,4-thiadiazol-2-yl)- p-nitrostyrene II) To 157 g. (1.0 mole) of 2-acetamido-5- methylthiadiazole and 151 g. (1.0 mole) of pnitrobenzaldehyde is added 1500 m1. of hot acetic anhydride and the mixture heated under reflux for 17 hours. The mixture is cooled, the yellow solid collected and washed thoroughly with acetone. After drying at 80C., for 17 hours under reduced pressure, 198.7 g. of

title compound is obtained. A sample purified from dimethylformamide-acetone mixture melts above 310C.

EXAMPLE 3 Preparation of S-Amino-l ,3,4-thiadiazole-2- carboxaldehyde (III) In 700 ml. of ethyl acetate, 20 g. (0.069 mole) of [3- (S-acetamido-l,3,4-thiadiazol-2-yl)-p-nitrostyrene is treated with ozone (4% in 0 stream, 0.08 moles per hr.) at 30 to 35C. for 2 hours to give a tan-colored suspension. The reaction mixture is purged of ozone with nitrogen for 20 minutes. To this, 60 g. of sodium iodide in 40 ml. glacial acetic acid and 400 ml. of water are added which are followed by 80 g. of sodium thiosulfate in 800 ml. of water. The organic layer is separated after500 ml. of ethyl acetate is added and the aqueous layer further extracted with 400 ml. of ethyl acetate. The extracts are dried over magnesium sulfate, filtered, and evaporated to give a yellow-brown sticky solid (20.5 g.). This material contains a mixture of p-nitrobenzaldehyde and 5-acetamido-l,3,4- thiadiazole-2-carboxaldehyde. The mixture is heated on a steam bath for 70 minutes with 19 ml. of concentrated hydrochloric acid and 20 ml. of glacial acetic acid. Evaporation of the acids under reduced pressure gives a yellow solid, which is treated with 300 ml. of percent hydrochloric acid to dissolve the aminothiadiazole aldehyde and the mixture is extracted twice with 200 ml. volumes of ethyl acetate to remove p-nitrobenzaldehyde. The aqueous acid phase is neutralized with sodium bicarbonate and then extracted with three 300 ml. volumes of ethyl acetate. These latter extracts are combined and dried over magnesium sulfate and evaporated to give 2.3 g. of solid yellow product (S-amino-l,3,4-thiadiazole-2-carboxaldehyde; infrared 11 max. (Nujol): 1688 cm. (C=0), NMR (acetone -d 1.831- (-NH and 0.04 'r CHO).

In a similar run, liquid-liquid extraction of the final aqueous phase with ethyl acetate gives a total yield of 4.1 g. of 5-amino-l,3,4-thiadiazole-2-carboxaldehyde, melting point 155-157C. (dec.)

EXAMPLE 4 Preparation of 5-Nitro-1,3,4-thiadiazole-2- carboxaldehyde (IV) 1.0 g. of S-amino-l ,3,4-thiadiazole-Z-carboxaldehyde is dissolved in a mixture of 2 ml. of 48-50 percent fluoboric acid and 5 ml. of water and added dropwise in about 20 minutes to a vigorously stirred suspension of 0.50 g. of copper powder in 2.0 g. of sodium nitrite in 10 ml. of water. The solution becomes green, foams, and a brown-yellow solid appears. The mixture is stirred for 30 minutes, filtered, and the insoluble solid washed with 50-75 ml. portions of hot chloroform EXAMPLE 5 Preparation of 3- {[(S-nitro-l ,3 ,4-thiadiazol-2- yl)methylene1-amino}-2-oxazolidinone (V) A solution of 2.1 g. (0.013 mole) of 5-nitro-2- thiadiazolecarboxaldehyde in 15 ml. of 95 percent ethanol is added to a solution of 1.53 g. (0.015 mole) of 3-amino-2-oxazolidinone in 10 ml. of 95 percent ethanol. The resulting solution is treated with 2 drops of concentrated hydrochloric acid and heated for 15 minutes on a steam bath. The yellow solid is collected and dried to give 1.1 g., melting point 248250C., of the title compound EXAMPLE 6 Preparation of 1-{[(5-nitro-1,3,4-thiadiazol-2- yl)methylene]-amino}-2-imidazolidinone (VI) A solution of 1.8 g. (0.011 mole) of 5-nitro-1,3,4- thiadiazole-2-carboxaldehyde in 20 ml. of 95% ethanol is added to 40 ml. of a 0.33 M solution of 1-amino-2- imidazolidinone in dilute sulfuric acid and the mixture heated on a steam bath. Water is added to the mixture until a clear solution is obtained and after 30 minutes of heating, it is cooled. The brown needles are collected and recrystallized from ml. of 67 percent aqueous ethanol to give 1.0 g. of yellow crystals, melting point 230-232C. of the title compound.

EXAMPLE 7 Preparation of S-nitro-l ,3,4-thiadiazole-2- carboxaldehyde thiosemicarbazone (VII) 5 g. (0.031 mole) of S-nitro-l,3,4-thiadiazole-2-carboxaldehyde is dissolved in 50 ml. of 95 percent ethanol and 3.6 g. (0.04 mole) of thiosemicarbazide in 50 ml. of 50 percent aqueous ethanol and 5 drops of concentrated hydrochloric acid are added. The mixture is heated at -95C. for 30 minutes, cooled, and the red solid collected. The yield of the title compound, melting point 290C., is 4.0 g.

EXAMPLE 8 Preparation of 2-Amino-5-(5-nitrol ,3,4-thiadiazol-2- yl)-1,3,4-thiadiazole (VIII) A suspension of 1.0 g. of S-nitro-Z-thiadiazolecarboxaldehyde thiosemicarbazone in a solution of 8.0 g. of ferric ammonium sulfate dodecahydrate in 20 ml. of water is heated at 90-95C. for 2 hours, cooled, and

the solid collected. The solid is recrystallized from 1:1 ethanol-acetone mixture which contains small amounts of dimethylformamide to give yellow crystals, melting point 240C. (dec.) of the title compound.

EXAMPLE 9 Preparation of 2-Methyl-5-nitro-l,3,4 thiadiazole (I) A solution of 2.78 g. (0.024 mole) of 2-methyl-5- aminothiadiazole in 17.5 ml. of 48-50 percent fluoboric acid is stirred at C. while 1.67 g. (0.024 mole) of sodium nitrite is added over 30 minutes. The mixture is stirred for 20 minutes at 0C. and then added dropwise to a vigorously stirred suspension of 4.9 g. of copper powder in a solution of 24.7 g. of sodium nitrite in 50 ml. of water at 25C. The mixture is stirred for 30 minutes, filtered, and the filter cake washed thoroughly with water. The combined filtrate and washings are extracted with three 150 ml. volumes of benzene. The combined extracts are dried and evaporated under reduced pressure to give 1.75 g., melting point 5455 C., of 2-methyl-5-nitro-1,3,4-thiadiazole.

EXAMPLE 10 Preparation of B-( 5 -Amino-1,3 ,4-thiadiazol-2-yl )-pnitrostyrene (X) A suspension of 5.0 g. of B-(5-acetamido-1,3,4- thiadiazol-Z-yl)-p-nitrostyrene in 20 ml. of concentrated hydrochloric acid and 20 ml. of glacial acetic acid is heated to reflux temperature for 2 hours. The

solid is collected, washed with ether, and dried to afford 4.4 g. of solid. This solid is washed with 25 ml. of 5 percent sodium bicarbonate solution and heated to 5055C. until foaming stops. The solid is collected, washed with water and dried to give 0.81 g. of yellow B- S-amino-l ,3,4-thiadiazol-2-yl)-p-nitrostyrene, melting point 284C. (dec.).

EXAMPLE 1 1 Preparation of S-Acetamido-l ,3 ,4-thiadiazole-2- carboxaldehyde (XI) EXAMPLE 12 Preparation of l-{[(5-Amino-1,3,4-thiadiazol-2- yl)methylene]-amino}-2-imidazolidinone (XII) The compound S-amino-l ,3,4-thiadiazole-2-carboxaldehyde (1.29 g. or 0.01 mole) is reacted with 1- amino-2-imidazolidinone in the manner described in Example 6 to give l-{[(5-amino-l,3,4-thiadiazol-2- yl)methylene]-amino}-2-imidazolidinone, which is collected as a pale yellow solid.

EXAMPLE 13 Preparation of 1- S-Acetamido-l ,3 ,4-thiadiazol-2- yl)-methylene]-amino}-2-imidazolidinone (XIII) To 1.71 g. (0.01 mole) of 5-acetamido-l,3,4-

thiadiazole-Z-carboxaldehyde in 20 ml. of percent ethanol is added to 40 ml. of a 0.33M solution of 1- amino-Z-imidazolidinone in the manner described in Example 6 to give solid l-{[(5-acetamido-1,3,4- thiadiazol-2-yl)methylene]amino}-2-imidazolidinone.

EXAMPLE 14 Preparation of 3-{[(5-acetamido-l ,3,4-thiadiazol-2- yl)methylene]-amino} -2-oxazolidinone (XIV) The compound 3-amino-2-oxazolidinone is reacted in equimolar amounts with S-acetamido-l ,3,4- thiadiazole-Z-carboxaldehyde in the manner described in Example 5 to give 3-{[(5-acetamido-l,3,4- thiadiazol-Z-yl)methylene]amino}-2-oxazolidinone, which is collected as an off-white solid.

EXAMPLE 15 Preparation of 3-{[(5-Amino-l ,3,4-thiadiazol-2- yl)methylene]-amino}-2-oxazolidinone (XV) Equimolar quantities of S-amino-l ,3,4-thiadiazole-2- carboxaldehyde and 3-amino-2-oxaaolidinone are reacted in the manner described in Example 5 to give 3-{ [(S-amino-l ,3 ,4-thia-diazol-2-yl)methylene]amino} -2-oxazolidinone, which is collected by filtration as a solid.

EXAMPLE 16 Preparation of S-Acetamido-l ,3,4-thiadiazole-2- carboxaldehyde thiosemicarbazone (XVI) 5 -Acetamido-l ,3 ,4-thiadiazole-2-carboxaldehyde is reacted with an equimolar quantity of thiosemicarbazide in the manner described in Example 7 to give the above compound, which is collected by filtration as a solid.

EXAMPLE 17 Preparation of 5 -Amino-1 ,3 ,4-

thiadiazolecarboxaldehyde thiosemicarbazone (XVII) In 15 ml. of 95 percent ethanol, 1.29 g. (0.01 mole) of S-amino-l,3,4-thiadiazole-2-carboxaldehyde and 0.92 g. of thiosemicarbazide are reacted in the manner described in Example 7 to give the above compound, which is collected by filtration as a solid.

EXAMPLE 18 Preparation of 2-Amino-5-(5-amino-l ,3,4-thiadiazol- 2-yl)-l ,3,4-thiadiazole (XVIII) The title compound is prepared in the manner described in Example 8 by cyclizing 2-amino-1,3,4- thiadiazole-2-carboxaldehyde thiosemicarbazone and collecting the product as a solid.

EXAMPLE 19 Preparation of 2-Acetamido-5-(5-acetamido-1,3,4- thiadiazol-Z-yl )-l ,3 ,4-thiadiazole (XIX) The compound 2-amino-5-(5-amino-l ,3 ,4- thiadiazol 2-yl)-l,3,4-thiadiazole is refluxed with acetic anhydride for one-half hour, evaporated to dryness, and the remaining solid washed with saturated aqueous sodium carbonate to give the title compound.

EXAMPLE 20 Preparation of 2-[2-(5-nitro-1 ,3,4-thiadiazol-2- yl)vinyl]quinoline (XX) In 3 ml. of glacial acetic acid at 6070C., 0.72 g. (Smmole) of freshly distilled quinaldine and 0.8 g. (mmole) of S-nitro-l,3,4-thiadiazole-Z-carboxaldehyde are stirred while 0.8 ml. of acetic anhydride is added dropwise. The mixture is refluxed for 4 hours, cooled, and the solvents are evaporated under reduced pressure. The remaining solid is washed with ether and collected by filtration to give the above compound.

EXAMPLE 21 Preparation of 2-[2-( S-acetamido-l ,3 ,4-thiadiazol-2- yl)vinyl]-quinoline (XXI) The title compound is prepared as described in Example 20 by reacting S-amino-l,3,4-thiadiazole-2-carboxaldehyde with quinaldine in the presence of acetic anhydride.

EXAMPLE 22 Preparation of 2-[2-(5-Amino-l ,3 ,4-thiadiazol-2- yl)vinyl]quinoline (XXII) The above compound is obtained by treating l g. of 2-[2-(5-acetamido-l ,3,4-thiadiazol-2-yl)vinyl1quinoline with 5 ml. of concentrated hydrochloric acid in 5 ml. of glacial acetic acid for 2 hours on a steam bath and neutralizing the mixture with saturated aqueous sodium carbonate solution. The solid product is collected by filtration and washed with water.

EXAMPLE 23 The antibacterial activity of the compounds of the present invention is demonstrated by the following tests wherein test compounds are dissolved in deionized water in sufficient amount to provide 100 ppm. of compound in the water. Test solutions are then sterilized and inoculated with a bacterial cell suspension of the test organism. The bacterial cell suspensions are 24 hour broth (0.1 percent dextrose 1.0 percent peptone) cultures that were inoculated with bacteria from 7-day Nutrient Agar Slants. After exposure for 24 hours, each test solution is treated with percent by volume of a 1 percent dextrose 10 percent peptone broth. The treated solutions are then incubated for 24 hours at 37C. and then examined for the presence or absence of bacterial growth. Determinations are made by turbidity readings. Solutions with no bacterial growth are subcultured to determine if the bacteria have been killed. Data are recorded as follows: 9 kill; 5 stasis; 0 no apparent effect.

Bacteria employed are Aerobacter aerogenes, a gram negative organism used by the Paper Institute to evaluate slime control agents for paper mills. Staphylococcus aureus, a gram positive common on the skins of man and animals and certain strains of which are pathogenic, and Xanthomonas vesicatoria, a gram negative organism whichincites bacteriosis of tomatoes and peppers.

Data obtained are provided in Table I.

TABLE I A. S. X. Compound Rate aerogenes aureus vesicaton'a NN u 9 9 OzN-k JCHZ s 0 0: g orr=N N NN 100 9 J U l i o om S CH=NII\IJ-KNH NN 100 9 0 5 O2N J- -K J-NH2 s s S 100 9 5 9 O2N\ -CH=N-NHC-NH2 EXAMPLE 24 The antifungal activity of the compounds of the invention is demonstrated by the following test wherein 7-10 day cultures of M. fructicola, 14 day cultures of S. sarcinaeforme and 7 day cultures of A. niger are separately washed from slants with deionized water and the suspensions filtered to remove large pieces of mycelium. Two ml. of orange juice are added per liter of spore suspension to facilitate germination. Optieular vials are then partially filled with the individual suspensions of test organism and a sufficient amount of aqueous solution or suspension of test compound added to provide 100 ppm. thereof to the test vials. The vials are placed on a tumbler and rotated for 24 hours to expose the organisms to the test compounds. At the end of a 24 hour exposure period the suspensions are examined macroscopically. Data are recorded as percent of the spores that have not germinated and are reported below.

TABLE II Rate M. frunc- S. sarcinas- A. ppm ticola forme niger As indicated above the organisms used are Monilinia fructicola, the pathogen that incites American brown rot of stone fruits; Stemphylium sarcinaeforme, the pathogen which incites leaf spot of legumes and Aspargillus niger, the saprophyte that degrades textiles, fabrics, leathers, fruits and vegetables.

Compound EXAMPLE 25 l-{[(S-Nitro-l,3,4-

thiadiazol-Z- I The antibacterial activity of the compounds of the nmq t l l I -2-ImIdazolInone 31 mcg/ml P.m. present Invention Is further demonstrated 1n the follow- 62 meg/nlC.X., M., Bib S.c. ing tests wherein trypticase soy agar plates are a 125 m g/ 8.0.. A.s-.

I A.f.,E.c.,S.g.,S.I., prepared containing 4 to 250 mcg./ml. of test comsa pounds. 250 meg/ml S.f.

The plates stored at room temperature over night 1,3,4-th'ad 1-2 I then are Inoculated with the desired cultures. After In- .thiadifi1 y 25o meg/ml ,4 f., Rm.

oculation the plates are permitted to dry, then inverted B- F thiadmzol-Z-yD-pand incubated-for 24 hours at 37C. After the incubanitmsyrene 125 meg/ml 3 tion the plates are examined and growth or no growth determinations made by comparison with growth conw claim; trol plates. The results are recorded and reported 1, A compound h i h f ul below in Table III as the minimum concentration (meg/ml.) required to prevent growth of the organism. NN Organisms employed are recorded below. i I 0 n -oII=N N GRAM POSITIVE BACTERIA S l 2 Abbreviation Name 13: wherein R is selected from the group consisting of 3.131 Bacillus thuringiensis amino, mtro and lower alkanoylamino and Z is selected 4. C.x. Cornynebacterium xerosis i M Micmcoccus from the group consisting of oxygen and 6. 8.21. Staphylococcus aureus 7. S.a. Streptocaccus agalactiae 8. S.f. Streptococcus faecalis /NH GRAM NEGATIVE BACTERIA I 2. The compound in accordance with claim 1, 3{[(5- Ambw" emes nitro-l ,3 ,4-thiadiazol-2-yl)methylene ]amino} -2-oxl0. A.f. Alcaligenes faecalis l l. B.b. Bordetella bronchiseptica azo mone' 12. E.c. Escherichia coli 3. The compound In accordance wIth claim 1, l-{[( 13. Pm. Pasteurella multocida 14's. salmonua cholemesui; mtro 1,3 4 thIadIazol 2 yl)methylene]ammo} 2 15. so. Salmonella dublin lmldalolldmonelg. gagmonega galliirlarum 4. The compound in accordance with claim 1, l-{[( amoneatypi sacchammym cerevmae am1no l.3,4 thIadIazol 2 yl)methylene]ammo} 2 I lmIdazolIdInone.

TABLE III 5. The compound in accordance with claim 1, l-'{[( S-acetamidol ,3 ,4-thiadiazol-2-yl)methylene]-amino}- Compound Dose Organisms Limidazolidinone v 5-Nitro-l,3,4- 40 thiadiazole-Z- 6. The compound In accordance with claim 1, 3-{[( caybo de yd S-acetamido-l ,3,4-thiadiazol-2-yl)methylene]-amino}- thiosemicarbazone 125 meg/ml S.t., S.c. 2 Oxazolidinone ihiadia zc i z- 7. The compound In accordance with claim 1, 3-{[( yl)methylene]amino} 2 oxawlidinone 125 meg/ml L CJWAJZPM- S-ammg:l,3 ,4-thIadIazol-2-yl)methylene]amIno} -2- 250 meg/ml B.c.,B.b.,S.c.,S.g., "lone.

8.1., S.c. a: 

2. The compound in accordance with claim 1, 3(((5-nitro-1,3,4-thiadiazol-2-yl)methylene)amino) -2-oxazolidinone.
 3. The compound in accordance with claim 1, 1-(((5-nitro-1,3,4-thiadiazol-2-yl)methylene)amino) -2-imidazolidinone.
 4. The compound in accordance with claim 1, 1-(((5-amino-1,3,4-thiadiazol-2-yl)methylene)amino) -2-imidazolidinone.
 5. The compound in accordance with claim 1, 1-(((5-acetamido-1, 3,4-thiadiazol-2-yl)methylene)-amino) -2-imidazolidinone.
 6. The compound in accordance with claim 1, 3-(((5-acetamido-1, 3,4-thiadiazol-2-yl)methylene)-amino)-2-oxazolidinone.
 7. The compound in accordance witH claim 1, 3-(((5-amino-1,3,4-thiadiazol-2-yl)methylene)amino)-2-oxazolidinone. 